The importance of methods for the synthesis of chiral compounds in high enantiomeric purity cannot be overstated. In 2001, single enantiomer drugs comprised 36% ($147 billion) of the total market of $410 billion. This number is projected to increase steadily, such that chiral drugs will constitute a market of over $200 billion by 2008. The growing economic importance of chiral compounds has spurred major research efforts from many laboratories, academic and industrial, directed at the selective preparation of chiral compounds. A recent report from the PI's laboratory described the development of chiral metal-salen complexes that are exceptional catalysts for enantioselective Diels-AIder (DA) reactions, one of the most useful reactions for organic synthesis. A major focus of the proposed activity will be to investigate these catalysts and to develop related complexes for use in DA and other C-C bond forming reactions. The high efficiency of these catalysts (record low catalyst loading) makes them attractive for various applications in complex molecule synthesis, even for industrial uses. In conjunction with this work, additional heteroatom-substituted dienes will be developed for use in DA reactions. Also presented in the proposal are plans for the development of metal-free catalysts that use hydrogen bonding rather than Lewis acids to promote the enantioselective process. This metal-free acceleration of reactions is not only of fundamental interest, but is also of potential industrial importance, since metal impurities, especially transition metals, are undesirable in precious chemicals such as pharmaceutical drugs. Effort will be directed at the use of hydrogen bonding for the enantioselective catalysis of various C-C bond-forming reactions. The asymmetric catalysis capabilities of numerous chiral alcohols as well as other hydrogen bond donors will be examined. Both of the major subprojects (metal salen complexes and hydrogen bonding catalysis) will integrate crystallographic studies and computational modeling in order to develop models to rationalize the observed enantioselectivities. Overall, the investigations described in this proposal are expected to lead to useful new methodology advances for the asymmetric synthesis of complex molecules. The projects described herein will provide excellent training for undergraduate students, graduate students, and postdoctoral associates in asymmetric catalysis methodology development and complex molecule synthesis, experience that will prepare them well for independent research careers, either in industry or academics. [unreadable] [unreadable]